Zobrazeno 1 - 10
of 13
pro vyhledávání: '"James, Devenny"'
Autor:
Jeffrey A. Robl, Michael Thomas, Mary Ann Pelleymounter, Brian Gemzik, Anthony V. Azzara, Brian J. Murphy, Sharon N. Bisaha, Helen E. Godonis, Daniel Longhi, Neil Flynn, William N. Washburn, Kenneth W. Rohrbach, Khehyong Ngu, Saleem Ahmad, Susan Harvey, Christine Huang, Evan B. Janovitz, Andres S. Hernandez, James Devenny, Hongwei Zhang, Lisa Zhang, Susan Glick, Suzanne Rooney, Wei Wang
Publikováno v:
Journal of Medicinal Chemistry. 59:8848-8858
The potent MCHR1 in vitro and in vivo antagonist activity of a series of cyclic tertiary alcohols derived from compound 2b is described. Subsequent pharmacokinetic and pharmacodynamic studies identified BMS-814580 (compound 10) as a highly efficaciou
Autor:
Neil Flynn, Mary Jane Cullen, Hongwei Zhang, Wei Wang, Susan Glick, Lisa Zhang, Jeffrey A. Robl, Pratik Devasthale, Andres S. Hernandez, Christian Caporuscio, Brian J. Murphy, Suzanne Rooney, Ning Huang, Mary Ann Pelleymounter, Kenneth W. Rohrbach, Kishore Renduchintala, Anthony V. Azzara, Helen E. Godonis, Yi-Xin Li, Radhakrishnan Sridhar, Michael Thomas, Susan Harvey, Paul Stetsko, Mary F. Grubb, Chris Freeden, Fang Moore, Christine Huang, James Devenny, Daniel Longhi, William N. Washburn
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 25:2793-2799
Our investigation of the structure–activity and structure–liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can i
Autor:
Jeffrey A. Robl, Guohua Zhao, Joel C. Barrish, Bei Wang, Brad D. Maxwell, Christian Caporuscio, Hongwei Zhang, James Devenny, Mary F. Grubb, Zhenghua Wang, Suzanne Rooney, James Mignone, Lisa Zhang, Brian J. Murphy, Wei Wang, Daniel Longhi, William N. Washburn, Kenneth W. Rohrbach, Evan B. Janovitz, Mark C. Manfredi, Mary Ann Pelleymounter, Michael Thomas, Hong Yang, Paul Stetsko, Saleem Ahmad, Atsu Apedo, Mary Jane Cullen, Brian Gemzik, Ning Huang, Chris Freeden, Susan Harvey, Anthony V. Azzara, Khehyong Ngu, Christine Huang, Rulin Zhao, Susan Glick, Neil Flynn, Pratik Devasthale, Andres S. Hernandez, Helen E. Godonis
Publikováno v:
Journal of Medicinal Chemistry. 57:7509-7522
Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us
Autor:
Kenneth E. Carlson, Olafur S. Gudmundsson, Bruce A. Ellsworth, Philip M. Sher, Susan Harvey, Eva Zuvich, Michael Thomas, William J. Keim, Gang Wu, Helen E. Godonis, Paul Stetsko, Brian J. Murphy, Richard B. Sulsky, Guixue Yu, William R. Ewing, Mary Jane Cullen, Mary Ann Pelleymounter, Doree F. Sitkoff, Susan Johnghar, Zhengxiang Gu, Ximao Wu, James Devenny, Rose Ann F Baska, Asoka Ranasinghe, Ning Lee, Kamelia Behnia, Anthony V. Azzara, Kenneth W. Rohrbach, Gerry Everlof, Liya Kang, Natesan Murugesan, Yeheng Zhu, Yifan Yang
Publikováno v:
Journal of Medicinal Chemistry. 56:9586-9600
Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set
Autor:
Saleem, Ahmad, William N, Washburn, Andres S, Hernandez, Sharon, Bisaha, Khehyong, Ngu, Wei, Wang, Mary Ann, Pelleymounter, Daniel, Longhi, Neil, Flynn, Anthony V, Azzara, Kenneth, Rohrbach, James, Devenny, Suzanne, Rooney, Michael, Thomas, Susan, Glick, Helen, Godonis, Susan, Harvey, Hongwei, Zhang, Brian, Gemzik, Evan B, Janovitz, Christine, Huang, Lisa, Zhang, Jeffrey A, Robl, Brian J, Murphy
Publikováno v:
Journal of medicinal chemistry. 59(19)
The potent MCHR1 in vitro and in vivo antagonist activity of a series of cyclic tertiary alcohols derived from compound 2b is described. Subsequent pharmacokinetic and pharmacodynamic studies identified BMS-814580 (compound 10) as a highly efficaciou
Autor:
Suzanne Rooney, James Devenny, Helen E. Godonis, Susan Harvey, Mary Jane Cullen, Mary Ann Pelleymounter
Publikováno v:
Obesity. 20:1645-1652
Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential fo
Autor:
Jahangir Iqbal, M. Mahmood Hussain, Ramakrishna Seethala, Luping Chen, Anthony V. Azzara, Mary Ann Pelleymounter, Ching-Hsuen Chu, Dong Cheng, Jessica Dong, William J. Keim, R. Michael Lawrence, James Devenny
Publikováno v:
Journal of Biological Chemistry. 283:29802-29811
Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of the four intestinal membrane bound acyltransferases implicated in dietary fat absorption. Recently, it was found that, in addition to acylating diacylglycerol (DAG), DGAT1 also posses
Autor:
Evan B. Janovitz, Mary Ann Pelleymounter, Mary F. Malley, Eva Zuvich, Jeffrey G. Varnes, Xueying Cao, Chen-Pin Hung, Karen A. Rossi, Mary Jane Cullen, Thao Ung, William J. Keim, Sarah E. Malmstrom, Michael Thomas, Keith J. Miller, Ginger Wu, Kenneth W. Rohrbach, Ge Zhang, Rangaraj Narayanan, Qinling Qu, Lois D. Lehman-McKeeman, Jeffrey A. Robl, James Devenny, Dean A. Wacker
Publikováno v:
Journal of Medicinal Chemistry. 50:1365-1379
Robust pharmaceutical treatment of obesity has been limited by the undesirable side-effect profile of currently marketed therapies. This paper describes the synthesis and optimization of a new class of pyrazinoisoindolone-containing, selective 5-HT2C
Autor:
Brian J. Murphy, James Devenny, Suzanne Rooney, Jagannath Selvaraj, James Mignone, Susan Glick, Sridhar Radhakrishnan, Helen E. Godonis, Neil Flynn, Rajesh Kuppusamy, Jayanthi Dhanapal, Mary Ann Pelleymounter, Chris Freeden, Pratik Devasthale, Daniel Longhi, William N. Washburn, Ning Huang, Christian Caporuscio, Mary F. Grubb, Paul Stetsko, Kenneth W. Rohrbach, Mary Jane Cullen, Christine Huang, Wei Wang, Susan Harvey, Hongwei Zhang, Lisa Zhang, Michael Thomas, Jeffrey A. Robl, Kishore Renduchintala, Anthony V. Azzara
Publikováno v:
Bioorganicmedicinal chemistry letters. 25(20)
Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki=1.8 nM), demonstrated
Autor:
Jeffrey A. Robl, Mary Jane Cullen, Guohua Zhao, Mary Ann Pelleymounter, Ginger Wu, Thao Ung, Keith J. Miller, Chet Kwon, Xueying Cao, Chen-Pin Hung, Kenneth W. Rohrbach, Philip D. Stein, Sarah E. Malmstrom, Jinping Gan, Qinling Qu, William J. Keim, Karen A. Rossi, James Devenny, Ge Zhang, Sharon N. Bisaha
Publikováno v:
Bioorganicmedicinal chemistry letters. 23(13)
The 5-HT2C receptor has been implicated as a critical regulator of appetite. Small molecule activation of the 5-HT2C receptor has been shown to affect food intake and regulate body weight gain in rodent models and more recently in human clinical tria